Substituent effects destabilizing effect

The gas and aqueous-phase basicities of pyrimidine are distinctly smaller by 3.4 and 1.1 pAi units, respectively, than those of pyridazine. A theoretical explanation has been proposed by considering important NH and lone pair electrostatic interactions that act from the 2-position. The proton-transfer equilibrium for the basicity comparison shows that the position of equilibrium is in the direction expected for the dominant effect to be the relief of the destabilization imparted by electrostatic repulsion between lone pair electrons, i.e., to the left in the equation (Equation (1)). Another significant contribution to AG° values is the field inductive effect of the electronegative aza substituent, which is less at the 3- than at the 2-position. This aza substituent effect destabilizes cations. Second-order attractive interactions between the lone pair electrons and the adjacent NH in the conjugate acid of pyridazine are also invoked. The attractive electrostatic interaction in the conjugate acid of pyridazine, and the predominant lone pair repulsion in pyridazine, are opposed by a favorable aza substituent effect. This accounts for the positive AG°(g) value. Solvation by water is expected to preferentially stabilize the neutral species or ion which is internally destabilized. The result is a smaller equilibrium shift in solution compared with the gas phase <86JA3237>. 

This is opposite from the order in solution as revealed by the pK data in water and DMSO shown in Table 4.14. These changes in relative acidity can again be traced to solvation effects. In the gas phase, any substituent effect can be analyzed directly in terms of its stabilizing or destabilizing effect on the anion. Replacement of hydrogen by alkyl substituents normally increases electron density at the site of substitution, but this effect cannot be the dominant one, because it would lead to an ordering of gas-phase acidity opposite to that observed. The dominant effect is believed to be polarizability. The methyl... 

The effect of substituents has been probed by MO calculations at the STO-3G level. An isodesmic reaction corresponding to transfer of a proton from a substituted <7-complex to an unsubstituted one will indicate the stabilizing or destabilizing effect of the substituent. The results are given in Table 10.1. 

Decide if ion-dipole interactions are responsible for the observed substituent effects. Obtain the charge on carbon and nitrogen in each cyano group. What evidence is there for a polar CN bond Should the ion (O )-dipole (CN) interaction be stabilizing or destabilizing Can these interactions explain the trends in electrostatic potential (Hint Focus on changes in O—CN distance and in orientation of the cyano group.)... 

Intramolecular hydrogen-bonds can increase the stability of certain conformations. For example, dianhydrides that contain fJ-L-Sorp or ct-D-Frup in the 5C2 conformation have the C-4 hydroxyl group in a 1,3-diaxial relationship with 0-2, which permits the formation of an intramolecular hydrogen bond. This might, in part, offset the destabilizing influence of three or two axial substituents, respectively. This effect is decreased in hydrogen-bonding solvents. 

Important literature is available for this type of ylides which are usually thermally stable in the case of phosphorus, arsenic or stilbene C-substituents. This is different for ylides C-substituted by nitrogen atoms which have a destabilizing effect. 

An EPR study of the monomeric 02 adducts of the Schiff base complexes of Co(bzacen)(py) (71a) and the thiobenzoyl analog Co(Sbzacen)(py) (71b) characterized the five-coordinate mono (pyridine) precursors and the six-coordinate 02 adducts.327 Increased covalency in the Co—S bonds was seen in the EPR parameters, indicative of 7r-backbonding. Substituent effects on the aromatic rings had no effect on the EPR spectra, but these were reflected in the observed redox potentials. Furthermore, the S-donors stabilize the Co ion in lower oxidation states, which was consistent with destabilization of the 02 adducts. 

Substituent effect on the stability of the transition state for solvent addition (C, Figure 6). The difference in the values of ks = 1.4 x 107s 1 for the addition of a solvent of 50/50 (v/v) trifluoroethanol/water to Me-[10+] and ks = 1.0 x 109 s-1 for addition of the same solvent to Me-[8+] (Table 1) reflects the balance between (1) the destabilization of X-[10+] resulting from rotation about the —Ca bond, which results in a less stable carbocation and hence an... 

Substituent effects on ks. The replacement of an a-methyl group at the 4-methoxycumyl carbocation CH3-[14+] by an a-ester or a-amide group destabilizes the parent carbocation by 7 kcalmol-1 relative to the neutral azide ion adduct (Scheme 11 and Table 3) and results in 5-fold and 80-fold decreases, respectively, in ks for nucleophilic addition of a solvent 50/50 (v/v) methanol/water.33 These results follow the trend that strongly electron-withdrawing substituents, which destabilize a-substituted 4-methoxybenzyl carbocations relative to neutral adducts to nucleophiles, do not lead to the expected large increases in the rate constants for addition of solvent.28,33,92-95... 

Electrical effects. These effects cause a variation in the electron density at the active site. They account for the ability of a substituent to stabilize or destabilize a cation, anion, radical, carbene or other chemical species. 

The substituent effects predicted for vinyl radicals are rather similar to those already observed for alkyl radicals (Table 4). Attachment of alkyl groups or it systems to the radical center stabilize the radical while the introduction of a-acceptors in the a- or / -position are destabilizing. The nature of the... 

Several attempts have been made to analyse the captodative effect through rotational barriers in free radicals. This approach seems to be well suited as it is concerned directly with the radical, i.e. peculiarities associated with bond-breaking processes do not apply. However, in these cases also one has to be aware that any influence of a substituent on the barrier height for rotation is the result of its action in the ground state of the molecule and in the transition structure for rotation. Stabilization as well as destabilization of the two states could be involved. Each case has to be looked at individually and it is clear that this will provide a trend analysis rather than an absolute determination of the magnitude of substituent effects. In this respect the analysis of rotational barriers bears similar drawbacks to all of the other methods. 

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